Infusion of Melatonin Into the Paraventricular Nucleus Ameliorates Myocardial Ischemia–Reperfusion Injury by Regulating Oxidative Stress and Inflammatory Cytokines

Figures

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  FIGURE 1.. Melatonin ameliorated MI/R injury by reducing myocardial infarct size and improving cardiac functional recovery. A, Evans blue/TTC double staining was performed 6 hours after reperfusion. The blue-stained portion indicates the nonischemic, normal region; the red-stained portion indicates I/R; and the negative-stained portion indicates the I/R infarcted region. B, Representative M-mode echocardiographic images. Cardiac function was assessed by using echocardiography 2 weeks after reperfusion. C, Myocardial infarct size expressed as percentage of the AAR. D, LVFS. E, LVEF. F, LVEDV. The results are expressed as mean values ± SEMs (n = 7). *P < 0.05 versus the sham group; †P < 0.05 MI/R + PVN Mel versus MI/R + PVN vehicle.

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  FIGURE 2.. Effects of PVN infusion of melatonin on plasma (A) and PVN (B) levels of NE in MI/R rats. Values are expressed as mean ± SEMs (n = 7). *P < 0.05 versus the sham group; †P < 0.05 MI/R + PVN Mel versus MI/R + PVN vehicle.

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  FIGURE 3.. Effects of PVN infusion of melatonin or vehicle on PVN levels of superoxide and Cu/Zn-SOD proteins in MI/R rats. A, Representative immunofluorescence image of fluorescent-labeled dihydroethidium (DHE) in the PVN in different groups. B, Representative immunoblots of Cu/Zn-SOD in the PVN in different groups. C, Densitometric analysis of the immunofluorescent intensity of DHE in the PVN in different groups. D, Densitometric analysis of protein expression of Cu/Zn-SOD in the PVN in different groups. Values are expressed as mean ± SEM (n = 7). *P < 0.05 versus the sham group; †P < 0.05 MI/R + PVN Mel versus MI/R + PVN vehicle.

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  FIGURE 4.. Effects of PVN infusion of melatonin on PVN levels of NOX2 in MI/R rats. A, Representative immunohistochemical staining of NOX2 in the PVN in different groups. B, Representative immunoblots of NOX2 in the PVN in different groups. C, Densitometric analysis of immunohistochemical intensity of NOX2 in the PVN in different groups. D, Densitometric analysis of protein expression of NOX2 in the PVN in different groups. Values are expressed as mean values ± SEMs (n = 7). *P < 0.05 versus the sham group; †P < 0.05 MI/R + PVN Mel versus MI/R + PVN vehicle.

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  FIGURE 5.. Effects of PVN infusion of melatonin on PVN levels of NOX4 in MI/R rats. A, Representative immunohistochemical staining of NOX4 in the PVN of the sham and MI/R groups. B, Representative immunoblots of NOX4 in the PVN of the sham and MI/R groups. C, Densitometric analysis of immunohistochemical intensity of NOX4 in the PVN of the sham and MI/R groups. D, Densitometric analysis of protein expression of NOX4 in the PVN of the sham and MI/R groups. Values are expressed as mean values ± SEMs (n = 7). *P < 0.05 versus the sham group; †P < 0.05 MI/R + PVN Mel versus MI/R + PVN vehicle.

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  FIGURE 6.. Effects of PVN infusion of melatonin on PVN levels of IL-1β and NF-κB p65 in MI/R rats. A, Representative immunohistochemical staining of IL-1β in the PVN of the sham and MI/R groups. B, Representative immunoblots of IL-1β in the PVN of the sham and MI/R groups. C, Densitometric analysis of immunohistochemical intensity of IL-1β in the PVN of the sham and MI/R groups. D, Densitometric analysis of protein expression of IL-1β in the PVN of the sham and MI/R groups. E, Effects of PVN infusion of melatonin on NF-κB p65 activation in the PVN of the sham and MI/R groups. Values are expressed as mean values ± SEMs (n = 7). *P < 0.05 versus the sham group; †P < 0.05 MI/R + PVN Mel versus MI/R + PVN vehicle.

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  FIGURE 7.. Effects of PVN infusion of melatonin on PVN levels of IL-10 in MI/R rats. A, Representative immunohistochemical staining of IL-10 in the PVN of the sham and MI/R groups. B, Representative immunoblots of IL-10 in the PVN of the sham and MI/R groups. C, Densitometric analysis of immunohistochemical intensity of IL-10 in the PVN of the sham and MI/R groups. D, Densitometric analysis of protein expression of IL-10 in the PVN of the sham and MI/R groups. Values are expressed as mean values ± SEMs (n = 7). *P < 0.05 versus the sham group; †P < 0.05 MI/R + PVN Mel versus MI/R + PVN vehicle.

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  FIGURE 8.. A schematic illustration of the proposed mechanism underlying the effects of melatonin on regulating PICs and ROS within the hypothalamic PVN in MI/R rats.